Studies now suggest that early sepsis, which is characterized by an excessive inflammatory response, may be followed by a period in which immunoresponsiveness and host defense is depressed. This depression is speculated to predispose the host to additional infection. Whether such a state exists and whether, if present, it is reversible with the administration of immunostimulatory agents is debated. Using a multifactorial study design in a rat model, we plan to study the effects of an initial episode of bacterial infection and sepsis on the host's susceptibility to later infection. As part of this same study, we also plan to study the effects of G-cerebrospinal fluid administration on later susceptibility to infection. Arrangements are under way to complete an MTA with Amgen so that these studies can proceed.